Pseudoxanthoma Elasticum (PXE) is a genetic disease characterized by elastic fiber calcification. This can result in disfiguring cutaneous and destructive occular and vascular lesions. Our preliminary studies suggest a relation between dairy product intake and severity of disease and have indicated a demineralization therapy for the disease. We find elastic fibers in involved dermis contain central polyanion-calcium phosphate deposits. Elastic fibers in uninvolved dermis also contain abnormal polyanions. Both involved and uninvolved dermis are characterized by abnormal fibroblasts, increased polyanion content and an increased calcium uptake in vitro. The clinical objectives of our proposed research are to use dietary surveys and mineral metabolic studies to evaluate further the effects of calcium, phosphate and vitamin D intake on the progression of PXE, to develop methods for identifying subclinical forms and genetic carriers of PXE, and to test the efficacy of rapid and slow demineralization in treatment of these patients. The objectives of studies of the basic defect are to isolate and characterize the polyanions in the elastic fibers, determine whether they are produced by fibroblasts, and determine their role in the calcification of elastic fibers and uptake of calcium by the dermis. These studies should increase knowledge of the lesion and of treatment of PXE and may provide better understanding and treatment of other more common crippling connective tissue diseases.